fibroblast growth factor 23 in chronic respiratory failure

Conditions: Chronic Respiratory Failure

Summary: fibroblast growth factor 23 (fgf23) is a key hormone of the mineral metabolism produced in bone and acting on the kidney to lower phosphatemia. fgf23 is subject to inactivating proteolytic cleavage which results in the presence of c-terminal and n-terminal fragments heretofore described as inactive. we recently showed an increase in fgf23ct in sickle cell patients, its association with left ventricular mass as well as a direct, pro-hypertrophic effect of fgf23ct on rat cardiomyocytes. data from the literature suggest that hypoxia (linked or not to anemia) is responsible for an increase in the production and cleavage of fgf23, either via the hypoxia inducible factor (hif1α) or via the increase in erythropoietin (epo). we hypothesize that the fgf23ct / fgf23i ratio is increased in response to chronic tissue hypoxia, in the absence of anemia, in patients with chronic respiratory failure (crf) either due to a direct response to hypoxia via the stimulation of hif1α, or indirectly via the increase in the circulating concentration of epo. this elevation, if proven, could contribute to the increased risk of heart disease seen in some populations of crf. we propose to test this hypothesis by assaying fgf23ct and fgf23i in a cohort of adult crf patients before and after initiation of oxygen therapy. the object of the present study is to study the fgf23ct / fgf23i ratio in incident patients presenting with a non treated crf as well as the modifications of this ratio under oxygen therapy and to study the correlations between fgf23 ct and fgf23 and i) oxygen saturation and pao2 ii) echocardiographic parameters and iii) epo concentrations. three visits are planned: baseline (before initiation of oxygen therapy), and two visits after initiation of oxygen therapy, at 3 months (m3) and at 12 months (m12). for each visit, anthropometric and clinical data, treatment and biological results will be collected. fgf23 intact , fgf23 c-terminal and erythropoietin will be measured. a cardiac ultrasound will be performed at baseline and at m12.


Eligibility criteria:
inclusion criteria: * patient informed and not opposed to participating in the research * age ≥ 18 years old * severe chronic respiratory failure defined by pao2 \<60 mmhg, whatever the cause, and justifying the initiation of long-term oxygen therapy * not yet treated or with stopping oxygen therapy for at least 6 weeks * be affiliated with a social security scheme or be a beneficiary of such a scheme * be able to understand the interest and the constraints of the study exclusion criteria: * exacerbation of respiratory failure in the 6 weeks prior to inclusion * chronic kidney disease defined by a glomerular filtration rate (gfr) estimated by ckd-epi \<60 ml / min / 1.73m2 * anemia at the time of inclusion whatever the cause (sickle cell anemia, thalassemia, hemolytic anemia, chronic iron deficiency, others) * pregnancy * breastfeeding women * simultaneous participation in another therapeutic trial * patient under guardianship or curatorship * patient under medical help from the french government

Keywords: fibroblast growth factor 23 erythropoietin cardiac hypertrophy pulmonary hypertension oxygen therapy chronic respiratory failure